Omega-3 as well as caloric restriction prevent the age-related modifications of cholesterol metabolism.
Intracellular concentration of cholesterol is regulated by the balance between endogenous synthesis and exogenous uptake; endogenous synthesis is subject to feedback control of hepatic 3-hydroxy-3-methyl-glutaryl-CoA reductase activity, while the exogenous supply is mainly controlled by the modulation of the low-density lipoprotein receptor. During ageing, hepatic lipid modifications occur and caloric restriction are able to prevent these changes. So, the aim of this work was to evaluate the mechanisms underlying the effect exerted both by caloric restrictions and by a diet enriched with Omega-3 fatty acids, on the cholesterol plasma levels during ageing, by studying the regulation of the protein involved in cholesterol homeostasis maintenance. Livers from diet restricted and Omega-3 supplemented diet fed 24-month-old rat were used to analyze, the protein complex of cholesterol homeostasis maintenance and those ones that are able to modulate 3-hydroxy-3-methyl-glutaryl-CoA reductase. The data obtained demonstrate that both caloric restriction and Omega-3 supplemented diets are able to prevent hypercholesterolemia, by regulating HMG-CoAR activation state by controlling ROS production and p38 phosphorylation. Moreover also the age-dependent loss of LDLr membrane exposition is prevented.
Martini
Chiara
C
Department of Biology, University of Roma Tre, Viale Marconi 446, 00146 Rome, Italy.
Pallottini
Valentina
V
De Marinis
Elisabetta
E
Marino
Maria
M
Cavallini
Gabriella
G
Donati
Alessio
A
Straniero
Sara
S
Trentalance
Anna
A
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000375:Aging / Q000097:blood / Q000378:metabolism*; D000818:Animals; D031204:Caloric Restriction; D002784:Cholesterol / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D006937:Hypercholesterolemia / Q000378:metabolism / Q000517:prevention & control; D008099:Liver / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D015525:Fatty Acids, Omega-3; D017382:Reactive Oxygen Species; D011973:Receptors, LDL; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases